Very low density lipoproteins (Beta-VLDL) are major initiators and propagators of atherosclerosis. Thus, plasma Beta-VLDL concentrations are associated with the production of atherosclerosis. The mechanism of atherogenesis could be attributable at least in part to Beta-VLDL greatly increasing cholesteryl ester content of cultured macrophages and causing their conversion to lipid-laden cells which resemble the foam cells of atherosclerotic lesions; macrophages are thought to be the cell type from which foam cells of plaques are derived. Recent work has identified structural and metabolic heterogeneity of Beta-VLDL. Two major subfractions have been identified on the basis of size. The larger particles of Beta-VLDL have been shown to be particularly potent stimulators of cholesterol esterification in cultured macrophages. Currently, little is known regarding in vivo metabolism of Beta-VLDL subfractions, or loci of tissue metabolism in vivo. Such information is of particular importance to delineate for arterial tissue. In the proposed study, Beta-VLDL will be harvested from diet-induced hypercholesterolemic rabbits. In vivo metabolism of Beta-VLDL subfractions will be characterized in normolipidemic rabbits and diet-induced and genetically-deficient hypercholesterolemic rabbits. Tissue and cellular metabolism of Beta-vLDL subfractions will be defined with radiolabels for the protein and cholesteryl ester moiety of the lipoproteins which remain untrapped within the cells that catabolize the lipoproteins. Using these techniques, the proposed in vivo study aims to determine the nature of Beta-VLDL subfraction particles as they are transferred from the lumen of the artery to arterial tissue, to define the regulation of cellular recognition of Beta-VLDL subfractions during diet-induced and genetically-determined hypercholesterolemia, and also to assess cell types of the aortic tissue which recognize the lipoprotein fractions. Such information will assist in determining the role of Beta-VLDL in the production of atherosclerosis and development of potential methods of preventing development of atherosclerosis.